Baicalin Alleviates ADAM17/EGFR Axis-Induced Peritonitis in Weaned Piglets Infected by Glaesserella parasuis

Simple SummaryGlaesserella parasuis(GPS), a Gram-negative bacterium that colonizes piglets’ upper respiratory tracts, causes Glässer’s disease including peritonitis under stress, though the peritonitis mechanism remains unclear. Baicalin, a main active component of Huangqin (Scutellaria baicalensis), exhibits significant anti-inflammatory effects. This study aimed to investigate the mechanism by which baicalin alleviatesGPS-induced peritonitis in piglets. We examined the effects of baicalin on inflammatory responses and key signaling molecules in both porcine peritoneal mesothelial cells (PPMCs) in vitro and the peritoneum ofGPS-infected piglets in vivo. Our results showed that baicalin significantly reducedGPS-induced expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6) and inhibited the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (ERK)/ERK. Mechanistically, baicalin inhibited ADAM17 overexpression-induced upregulation of this pathway and cytokines in PPMCs, while ADAM17 small interfering RNA attenuatedGPS-induced effects. These findings demonstrate that baicalin mitigatesGPS-induced peritonitis by suppressing the ADAM17/EGFR axis and the subsequent cytokine production, thus providing a theoretical basis for novelGPScontrol strategies and the development of novel non-antibiotic strategies, including phytochemical therapeutics and feed additives.Glaesserella parasuis(GPS) is a Gram-negative, pathogenic bacterium that colonizes the upper respiratory tract of piglets and causes Glässer’s disease with peritonitis under stress conditions. The mechanism underlying GPS-induced peritonitis in piglets remains unclear. Baicalin is one of the main active ingredients of Huangqin (Scutellaria baicalensis), which has a significant anti-inflammatory effect on inflammatory diseases. Therefore, this study aimed to elucidate the molecular mechanism by which baicalin alleviatesGPS-induced peritonitis in piglets, specifically focusing on the role of the ADAM17/EGFR signaling axis. We investigated the effects of baicalin in vitro using porcine peritoneal mesothelial cells (PPMCs) and in vivo in GPS-infected piglets. Our results showed that baicalin reduced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in PPMCs and the peritoneum of piglets afterGPSinfection. Concurrently, baicalin significantly reduced the upregulation of disintegrin and metalloproteinase 17 (ADAM17), phosphorylated epidermal growth factor receptor (p-EGFR)/EGFR, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK induced byGPSinfection in PPMCs and the peritoneum of piglets. Crucially, in vitro mechanistic investigations revealed that baicalin can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced by ADAM17 overexpression in PPMCs. Furthermore, ADAM17 small interfering RNA can significantly reduce the upregulation of ADAM17, p-EGFR/EGFR, p-ERK/ERK, TNF-α, IL-1β, and IL-6 induced byGPSinfection in PPMCs. These findings demonstrate that baicalin can inhibit the expression of inflammatory factors TNF-α, IL-1β, and IL-6 through the ADAM17/EGFR axis, and then alleviate the peritonitis caused byGPSin piglets. This provides a theoretical basis for developing novel non-antibiotic strategies, including phytochemical therapeutics and feed additives, for preventing and controlling GPS.